The Cac1 subunit of histone chaperone CAF-1 organizes CAF-1-H3/H4 architecture and tetramerizes histones.

The histone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4)2 histones onto newly-synthesized DNA during DNA replication. To understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the protein-protein interactions within the CAF-1-H3/H4 architecture using biophysical and biochemical approaches. Hydrogen/deuterium exchange and chemical cross-linking coupled to mass spectrometry reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicate that the Cac1 subunit functions as a scaffold within the CAF-1-H3/H4 complex. Cac1 alone not only binds H3/H4 with high affinity, but also promotes histone tetramerization independent of the other subunits. Moreover, we identify a minimal region in the C-terminus of Cac1, including the structured winged helix domain and glutamate/aspartate-rich domain, which is sufficient to induce (H3/H4)2 tetramerization. These findings reveal a key role of Cac1 in histone tetramerization, providing a new model for CAF-1-H3/H4 architecture and function during eukaryotic replication

Construção de um protótipo de Data Warehouse como suporte ao sistema de informação numa instituição de ensino superior

Uma das dificuldades que se verifica na extracção de informação numa organização é a falta de integração dos dados existentes dispersos em diversos formatos: ficheiros de processadores de texto, folhas de cálculo, bases de dados, entre outras fontes. A partir deste problema, este trabalho propõe a estruturação de um modelo de Data Warehouse com o objectivo de organizar, armazenar e integrar as informações provenientes de outros formatos e sistemas, numa única base de dados para uma futura utilização no suporte à tomada de decisão. Existem, neste momento, na comunidade de Data Warehousing duas principais abordagens, uma preconizada por William H. Inmon, mais centrada nos dados, e outra por Ralph Kimball, mais centrada no projecto. Assim, com a metodologia proposta foi desenvolvido um caso de estudo com a finalidade de verificar e avaliar a aplicabilidade da metodologia no Instituto Politécnico de Tomar; ABSTRACT: One difficulty that exists in the extraction of information in organizations is the lack of integration of existing data scattered in various formats: word processing files, spreadsheets, databases, among other sources. From this problem, this paper proposes to structure a model of Data Warehouse in order to organize, store and integrate information from other systems and formats in a single database for future use in supporting decision making. There are at present in the community of Data Warehousing two main approaches, one advocated by William H. Inmon, more data-centric, and one by Ralph Kimball, more focused on the project. So with the proposed methodology was developed a case study in order to verify and evaluate the applicability of the methodology at the Polytechnic Institute of Tomar

Structure-Function Studies On Novel Signaling Regulators

This dissertation studies the structures and functions of novel signaling regulators, with Chapter 2-4 focusing on sirtuins and Chapter 5 on the DOCK180 family of Rho GEFs. Sirtuins are NAD-dependent deacetylases that regulate important biological processes. Mammals have seven sirtuins, SIRT1-7. SIRT4-7 have undetectable or weak deacetylase activity. In Chapter 2 we identified SIRT5 as an efficient protein lysine desuccinylase and demalonylase. The preference for succinyl and malonyl groups is accomplished by their interactions with residue Tyr102 and Arg105 of SIRT5. Lysine malonylation and succinylation were identified in mammalian proteins. Additionally, SIRT5 can reverse succinylation in vivo. In Chapter 3 I delineated the desuccinylation reaction of SIRT5 in crystals, including the complex structure of SIRT5 with a bicyclic intermediate. The SIRT5 complex structures will provide insights to the design of SIRT5-specific inhibitors to investigate its biological functions. In Chapter 4, we investigated a sirtuin homologue from the malaria parasite Plasmodium falciparum, PfSir2A, which regulates the expression of surface antigens to evade the detection by host immune surveillance. We present enzymology and structural evidence supporting that PfSir2A preferentially hydrolyzes medium and long chain fatty acyl groups from lysine residues. This would facilitate the development of PfSir2A inhibitors as potential drugs in malaria treatment. As the Guanine nucleotide Exchange Factors (GEFs) of Rho GTPases, the DOCK180 family proteins are key regulators of cell motility, phagocytosis, and adhesion. Mammals have 11 members, DOCK1-11, which are classified into four subfamilies, A through D. The DOCK-C subfamily that includes DOCK6-8 has been proposed to activate both Cdc42 and Rac1. In Chapter 5 I show that DOCK7 promotes very weak activation of non-prenylated Cdc42 or Rac1 in solution, but robust activation of prenylated Cdc42 and Rac1 on model liposomes, demonstrating that the prenylation and membrane localization of GTPases are essential for the activation by DOCK7. Additionally, DOCK7 harbors residues that impart GTPase specificity and these can be mutated to shift a given DOCK7 activity profile. Finally, the DOCK7 possesses a distal site that binds preferentially to the active forms of Cdc42 and Rac1 and thereby forms a possible positive feedback loop in activating GTPases

MASTER: Multi-task Pre-trained Bottlenecked Masked Autoencoders are Better Dense Retrievers

Pre-trained Transformers (\eg BERT) have been commonly used in existing dense retrieval methods for parameter initialization, and recent studies are exploring more effective pre-training tasks for further improving the quality of dense vectors. Although various novel and effective tasks have been proposed, their different input formats and learning objectives make them hard to be integrated for jointly improving the model performance. In this work, we aim to unify a variety of pre-training tasks into the bottlenecked masked autoencoder manner, and integrate them into a multi-task pre-trained model, namely MASTER. Concretely, MASTER utilizes a shared-encoder multi-decoder architecture that can construct a representation bottleneck to compress the abundant semantic information across tasks into dense vectors. Based on it, we integrate three types of representative pre-training tasks: corrupted passages recovering, related passages recovering and PLMs outputs recovering, to characterize the inner-passage information, inter-passage relations and PLMs knowledge. Extensive experiments have shown that our approach outperforms competitive dense retrieval methods. Our code and data are publicly released in \url{https://github.com/microsoft/SimXNS}.Comment: Accepted by ECML-PKDD 2023, 16 page

Bamboo as a Nature-Based Solution (NbS) for Climate Change Mitigation: Biomass, Products, and Carbon Credits

Bamboo, a rapidly growing woody grass prevalent in pan-tropical zones, holds promising potential as a nature-based solution (NbS) for climate change mitigation. In this systematic review of 91 research articles, we critically assess the scope and constraints of bamboo’s role in mitigating climate change across three dimensions: as a carbon sink in biomass form, as carbon storage in bamboo products, and as a contributor to carbon project credits. Our analysis reveals that existing studies disproportionately focus on 36 limited species, such as Phyllostachys pubescens and Bambusa vulgaris, with geographic concentration in Asia (91%) and limited studies from Africa (7%) and South America (1%). While many studies emphasize the carbon-saving benefits of bamboo products compared with traditional goods, there is a noticeable gap in comprehensive evaluations of carbon pools from individual bamboo forests encompassing all product varieties. While bamboo forests offer significant carbon trading potential, their global role is restricted by the absence of internationally accepted methodologies and the presence of debates about classifying bamboo as a tree species. This extensive review highlights the multifaceted value of bamboo in climate change mitigation, thereby highlighting its significance as a critical component for informed policymaking and the development of sustainable practices in future climate strategies worldwide.Forestry, Faculty ofNon UBCReviewedFacultyResearche

<i>Plasmodium falciparum</i> Sir2A Preferentially Hydrolyzes Medium and Long Chain Fatty Acyl Lysine

<i>Plasmodium falciparum</i> Sir2A (PfSir2A), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, has been shown to regulate the expression of surface antigens to evade the detection by host immune surveillance. It is thought that PfSir2A achieves this by deacetylating histones. However, the deacetylase activity of PfSir2A is weak. Here we present enzymology and structural evidence supporting that PfSir2A catalyzes the hydrolysis of medium and long chain fatty acyl groups from lysine residues more efficiently. Furthermore, <i>P. falciparum</i> proteins are found to contain such fatty acyl lysine modifications that can be removed by purified PfSir2A <i>in vitro</i>. Together, the data suggest that the physiological function of PfSir2A in antigen variation may be achieved by removing medium and long chain fatty acyl groups from protein lysine residues. The robust activity of PfSir2A would also facilitate the development of PfSir2A inhibitors, which may have therapeutic value in malaria treatment